Abstract
The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×103 to 8×105 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.
Highlights
Pathogenic Leptospira species are globally distributed spirochetes that cause 350,000–500,000 severe human infections annually with an incidence of .10 cases per 100,000 population in humid, subtropical regions of the world and a mortality rate of 10% [1,2,3]
Serovars of Leptospira interrogans carried by rats cause life-threatening hepatorenal failure and pulmonary hemorrhage syndromes in tropical regions, especially where heavy rainfall occurs in urban areas with poor sanitation and flood control infrastructure [10]
Human infections caused by the bacterium, Leptospira interrogans, frequently result in a lifethreatening illness characterized by jaundice and kidney failure
Summary
Pathogenic Leptospira species are globally distributed spirochetes that cause 350,000–500,000 severe human infections annually with an incidence of .10 cases per 100,000 population in humid, subtropical regions of the world and a mortality rate of 10% [1,2,3]. These figures are likely to be underestimates because leptospirosis is a neglected tropical disease that occurs more commonly among medically underserved populations [4,5]. There is an urgent need for development of novel vaccine strategies that provide safe, longterm, cross-protective immunity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
